Renaud La Joie1, Alexandre Bejanin2, Anne M Fagan2, Nagehan Ayakta2, Suzanne L Baker2, Viktoriya Bourakova2, Adam L Boxer2, Jungho Cha2, Anna Karydas2, Gina Jerome2, Anne Maass2, Ashley Mensing2, Zachary A Miller2, James P O'Neil2, Julie Pham2, Howard J Rosen2, Richard Tsai2, Adrienne V Visani2, Bruce L Miller2, William J Jagust2, Gil D Rabinovici2. 1. From the Memory and Aging Center (R.L.J., A.B., N.A., V.B., A.L.B., J.C., A.K., A.M., Z.A.M., J.P., H.J.R., R.T., A.V., B.L.M., G.D.R.), University of California San Francisco; Knight Alzheimer's Disease Research Center (A.M.F., G.J.), Department of Neurology (A.M.F., G.J.), and The Hope Center for Neurological Disorders (A.M.F., G.J.), Washington University in St. Louis, MO; Molecular Biophysics and Integrated Bioimaging Division (S.L.B., J.P.O., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley, CA; and Helen Wills Neuroscience Institute (A.M., W.J.J., G.D.R.), University of California Berkeley. Renaud.Lajoie@ucsf.edu. 2. From the Memory and Aging Center (R.L.J., A.B., N.A., V.B., A.L.B., J.C., A.K., A.M., Z.A.M., J.P., H.J.R., R.T., A.V., B.L.M., G.D.R.), University of California San Francisco; Knight Alzheimer's Disease Research Center (A.M.F., G.J.), Department of Neurology (A.M.F., G.J.), and The Hope Center for Neurological Disorders (A.M.F., G.J.), Washington University in St. Louis, MO; Molecular Biophysics and Integrated Bioimaging Division (S.L.B., J.P.O., W.J.J.), Lawrence Berkeley National Laboratory, Berkeley, CA; and Helen Wills Neuroscience Institute (A.M., W.J.J., G.D.R.), University of California Berkeley.
Abstract
OBJECTIVE: To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample. METHODS: Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([18F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ42, total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3). Receiver operator characteristic analyses were performed to compare discrimination of Aβ-positive AD from non-AD conditions across biomarkers. Correlations between CSF biomarkers and PET standardized uptake value ratios (SUVR) were assessed using skipped Pearson correlation coefficients. Voxelwise analyses were run to assess regional CSF-PET associations. RESULTS: [18F]AV1451-PET cortical SUVR and p-tau showed excellent discrimination between Aβ-positive AD and non-AD conditions (area under the curve 0.92-0.94; ≤0.83 for other CSF measures), and reached 83% classification agreement. In the full sample, cortical [18F]AV1451 was associated with all CSF biomarkers, most strongly with p-tau (r = 0.75 vs 0.57 for t-tau and -0.49 for Aβ42). When restricted to Aβ-positive patients with AD, [18F]AV1451 SUVR correlated modestly with p-tau and t-tau (both r = 0.46) but not Aβ42 (r = 0.02). On voxelwise analysis, [18F]AV1451 correlated with CSF p-tau in temporoparietal cortices and with t-tau in medial prefrontal regions. Within AD, Mini-Mental State Examination scores were associated with [18F]AV1451-PET, but not CSF biomarkers. CONCLUSION: [18F]AV1451-PET and CSF p-tau had comparable value for differential diagnosis. Correlations were robust in a heterogeneous clinical group but attenuated (although significant) in AD, suggesting that fluid and imaging biomarkers capture different aspects of tau pathology. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, in a clinical sample of patients with a variety of suspected neurodegenerative diseases, both CSF p-tau and [18F]AV1451 distinguish AD from non-AD conditions.
OBJECTIVE: To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample. METHODS: Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([18F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ42, total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3). Receiver operator characteristic analyses were performed to compare discrimination of Aβ-positive AD from non-AD conditions across biomarkers. Correlations between CSF biomarkers and PET standardized uptake value ratios (SUVR) were assessed using skipped Pearson correlation coefficients. Voxelwise analyses were run to assess regional CSF-PET associations. RESULTS: [18F]AV1451-PET cortical SUVR and p-tau showed excellent discrimination between Aβ-positive AD and non-AD conditions (area under the curve 0.92-0.94; ≤0.83 for other CSF measures), and reached 83% classification agreement. In the full sample, cortical [18F]AV1451 was associated with all CSF biomarkers, most strongly with p-tau (r = 0.75 vs 0.57 for t-tau and -0.49 for Aβ42). When restricted to Aβ-positive patients with AD, [18F]AV1451 SUVR correlated modestly with p-tau and t-tau (both r = 0.46) but not Aβ42 (r = 0.02). On voxelwise analysis, [18F]AV1451 correlated with CSF p-tau in temporoparietal cortices and with t-tau in medial prefrontal regions. Within AD, Mini-Mental State Examination scores were associated with [18F]AV1451-PET, but not CSF biomarkers. CONCLUSION: [18F]AV1451-PET and CSF p-tau had comparable value for differential diagnosis. Correlations were robust in a heterogeneous clinical group but attenuated (although significant) in AD, suggesting that fluid and imaging biomarkers capture different aspects of tau pathology. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, in a clinical sample of patients with a variety of suspected neurodegenerative diseases, both CSF p-tau and [18F]AV1451 distinguish AD from non-AD conditions.
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